• Title/Summary/Keyword: MHC-class I

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Cyclooxygenase Inhibitors, Aspirin and Ibuprofen, Inhibit MHC-restricted Antigen Presentation in Dendritic Cells

  • Kim, Hyun-Jin;Lee, Young-Hee;Im, Sun-A;Kim, Kyungjae;Lee, Chong-Kil
    • IMMUNE NETWORK
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    • v.10 no.3
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    • pp.92-98
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    • 2010
  • Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve pain, reduce fever and inhibit inflammation. NSAIDs function mainly through inhibition of cyclooxygenase (COX). Growing evidence suggests that NSAIDs also have immunomodulatory effects on T and B cells. Here we examined the effects of NSAIDs on the antigen presenting function of dendritic cells (DCs). Methods: DCs were cultured in the presence of aspirin or ibuprofen, and then allowed to phagocytose biodegradable microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using OVA-specific CD8 and CD4 T cells. Results: Aspirin and ibuprofen at high concentrations inhibited both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens. Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs. Ibuprofen rather increased the expression level of total MHC molecules and co-stimulatory molecules on DCs. Conclusion: These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.

Effect of Bu-Zhong-Yi-Qi-Tang on Proliferation of T Cells (보중익기탕의 T세포 증식 유도 효과)

  • 채수연;신성해;하미혜;조성기;김성호;변명우;이성태
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.7
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    • pp.1085-1091
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    • 2004
  • Bu-Zhong-Yi-Qi- Tang extracts is a traditional oriental medicine in a mixture type exhibiting strong anti-bacterial, analgesic, and chemopreventive activities. In this study, we have evaluated effects of the total and polysaccharide fraction of Bu-Zhong-Yi-Qi- Tang extracts on the T cell proliferation, cytokine production, and induction of IL-2 receptor and MHC class n. For this experiment, we established CD4$^{+}$ CD8$^{[-10]}$ T cell line producing IL-2 and IFN-${\gamma}$ when stimulated with ovalbumin antigen in the presence of antigen presenting cells. The significant effect of Bu-Zhong-Yi-Qi-Tang on antigen-induced T cell proliferation in the presence of antigen presenting cells was observed. The proliferation and IFN-${\gamma}$ production of T cells was increased in a dose dependent manner, and expression of IL-2 receptor on T cells and MHC class n molecule on antigen presenting cells was also induced in the presence of Bu-Zhong-Yi-Qi-Tang polysaccharide fraction. It was demonstrated that polysaccharide fraction of Bu-Zhong-Yi-Qi-Tang stimulates the antigen-induced T cell proliferation and the production of IFN-${\gamma}$ possibly through the increase of IL-2 receptor and MHC class n expression. Therefore Bu-Zhong-Yi-Qi-Tang can be regarded as a natural and useful immunomodulator having a relatively nonotoxic property. Further studies are needed to better characterize the nature of Bu-Zhong- Yi-Qi-Tang extract.

Proteomic analysis of human serum from patients with temporal lobe epilepsy (측두엽 간질환자의 혈청에서 프로테오믹스기법을 활용한 질병관련 단백질 동정)

  • Lee, Chang Woo;Yu, Seung Taek;Choi, Ha Young;Koh, Bun Jeong;Kwak, Yong Guen
    • Clinical and Experimental Pediatrics
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    • v.52 no.5
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    • pp.567-575
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    • 2009
  • Purpose : Epilepsy affects more than 0.5% of the world's population. It has a large genetic component and is caused by electrical hyperexcitability in the central nervous system. Despite its prevalence, the disease lacks definitive diagnostic serological biomarkers. To identify potential biomarkers for epilepsy by a convenient method, we analyzed the expression of serum proteins, reflecting alterations in the patient's proteomes. Methods : We compared two-dimensional electrophoretic band patterns of human sera from eight patients with temporal lobe epilepsy (TLE) with those of eight control subjects. The differentially expressed bands were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and electrospray ionization quadrupole time-of-flight mass spectrometry. esults : Twelve proteins were differentially expressed in the TLE group, of which 6 were identified. Expression of haptoglobin Hp2, PRO2675, immunoglobulin heavy chain constant region gamma 2, an unnamed protein, and three unidentified proteins were upregulated in serum from the patients with TLE, whereas those of major histocompatibility complex (MHC) class I antigen, plasma retinol-binding protein precursor, and three unidentified proteins were downregulated in these patients. After resection of the epileptogenic zone, the expressions of MHC class I antigen, immunoglobulin heavy chain constant region gamma 2, two of the downregulated unidentified proteins, and one of the upregulated unidentified proteins returned to the normal range. Conclusion : The 12 serum proteins in this study are potentially useful biomarkers for the diagnosis and monitoring of TLE.

The Interaction between HCV-Infected huh7.5 Cells and HCV-Specific T Cells (C형 간염 바이러스 감염 간암 세포주와 T 림프구의 상호작용에 대한 연구)

  • Kang, Hyojeung;Cho, Hyosun
    • Korean Journal of Microbiology
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    • v.50 no.2
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    • pp.169-172
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    • 2014
  • Recently, Hepatitis C virus (HCV) replication system has been established using human hepatoma cells (huh cell) and a variety of HCV clones. In this study, we established an infectious HCV replication system using huh7.5 cells and J6/JFH1 clone (genotype 2a). In addition, we investigated the antigen presentation capability of HCV-infected huh7.5 cells to HCV-specific T cells. Interestingly, HCV-infected huh7.5 cells were not capable of activating HCV-specific T cells. However, huh7.5 cells stimulated by exogenous HCV peptide were able to activate HCV-specific T cells, which was shown to produce TNF-${\alpha}$ and IFN-${\gamma}$. We further examined if HCV infection has an inhibitory effect on the expression of MHC class I molecule of huh7.5 cells. We found that HCV infection did not change the expression level of MHC class I molecule on huh7.5 cells.

Characteristics and Improving Breed of Economic Traits of Korea Native Chicken (한국 재래 닭 품종 특성 및 초기성장 개량을 위한 분자표지 개발)

  • Oh J. D.;Park M. H.;Kong H. S.;Lee H. K.;Jeon G. J.;Yeon S. H.;Sang B. D.;Choi C. H.;Cho B. W.
    • Korean Journal of Poultry Science
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    • v.32 no.1
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    • pp.29-34
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    • 2005
  • This study was conducted to estimate the effects of genotype for chicken major histocompatibility complex (MHC) B-LB genes on economic traits. To detect polymorphism, 400 bp fragments of MHC B-LB genes were obtained and sequenced. After digestions using restriction enzyme Hea III, two restriction enzyme sites were observed. There were two mutations at position 427 and 651 those were decided as Type I and Type II, respectively. Using RFLP analyses, type I were genotyped to TT, TC and CC, and type II to MM, Mm and mm. The relatively higher TC genotype frequencies (0.8) of Type I and Mm genotype frequencies (0.88) of Type II were observed in Korean native chickens. The effects of the genotype on 150 days body weight trait were investigated by the associations of CC and Mm genotypes (P<0.05) in Korean native chickens. This result suggests that a significant association exists between the SNP and 150 days body weight.

Use of Cell-Penetrating Peptides in Dendritic Cell-Based Vaccination

  • Sangho Lim;Ja-Hyun Koo;Je-Min Choi
    • IMMUNE NETWORK
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    • v.16 no.1
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    • pp.33-43
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    • 2016
  • Cell-penetrating peptides (CPPs) are short amino acids that have been widely used to deliver macromolecules such as proteins, peptides, DNA, or RNA, to control cellular behavior for therapeutic purposes. CPPs have been used to treat immunological diseases through the delivery of immune modulatory molecules in vivo. Their intracellular delivery efficiency is highly synergistic with the cellular characteristics of the dendritic cells (DCs), which actively uptake foreign antigens. DC-based vaccines are primarily generated by pulsing DCs ex vivo with various immunomodulatory antigens. CPP conjugation to antigens would increase DC uptake as well as antigen processing and presentation on both MHC class II and MHC class I molecules, leading to antigen specific CD4+ and CD8+ T cell responses. CPP-antigen based DC vaccination is considered a promising tool for cancer immunotherapy due to the enhanced CTL response. In this review, we discuss the various applications of CPPs in immune modulation and DC vaccination, and highlight the advantages and limitations of the current CPP-based DC vaccination.

Analysis of Swine Leukocyte Antigen Haplotypes in Yucatan Miniature Pigs Used as Biomedical Model Animal

  • Choi, Nu-Ri;Seo, Dong-Won;Choi, Ki-Myung;Ko, Na-Young;Kim, Ji-Ho;Kim, Hyun-Il;Jung, Woo-Young;Lee, Jun-Heon
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.3
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    • pp.321-326
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    • 2016
  • The porcine major histocompatibility complex (MHC) is called swine leukocyte antigen (SLA), which controls immune responses and transplantation reactions. The SLA is mapped on pig chromosome 7 (SSC7) near the centromere. In this study, 3 class I (SLA-1, SLA-3, and SLA-2) and 3 class II (DRB1, DQB1, and DQA) genes were used for investigation of SLA haplotypes in Yucatan miniature pigs in Korea. This pig breed is a well-known model organism for biomedical research worldwide. The current study indicated that Korean Yucatan pig population had 3 Class I haplotypes (Lr-4.0, Lr-6.0, and Lr-25.0) and 3 class II haplotypes (Lr-0.5, Lr-0.7, and Lr-0.25). The combinations of SLA class I and II haplotype together, 2 homozygous (Lr-4.5/4.5 and Lr-6.7/6.7) and 3 heterozygous (Lr-4.5/6.7, Lr-4.5/25.25, and Lr-6.7/25.25) haplotypes were identified, including previously unidentified new heterozygous haplotypes (Lr-4.5/4.7). In addition, a new SLA allele typing method using Agilent 2100 bioanalyzer was developed that permitted more rapid identification of SLA haplotypes. These results will facilitate the breeding of SLA homozygous Yucatan pigs and will expedite the possible use of these pigs for the biomedical research, especially xenotransplantation research.

Clinico-Pathological Significance of MHC-I Type Chain-associated Protein A Expression in Oral Squamous Cell Carcinoma

  • Wang, Jie;Li, Chao;Yang, Dan;Jian, Xin-Chun;Jiang, Can-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.2
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    • pp.715-718
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    • 2012
  • The current research concerns the clinicopathological significance of MHC class I chain-related protein A (MICA) expression in oral squamous cell carcinomas (OSCCs). The expression and location of MICA protein in 14 normal oral mucous and 45 cancerous and para-cancerous tissues were assessed by immunohistochemistry and levels of MICA mRNA expression in 29 cancerous and para-cancerous tissues were determined by the real-time polymerase chain reaction. Data were analyzed with the SPSS16.0 software package. MICA was found to be located in the cytoplasm and plasma membrane. Expression was higher in para-cancerous than in cancerous tissues (P < 0.05). However, no statistical difference was found between the following: 1) para-cancerous tissue with normal mucosa; 2) normal mucosa with cancerous tissue;and 3) among different clinicopathological parameters in OSCC (P > 0.05). The level of MICA mRNA was higher in OSCCs than in para-cancerous tissues, and was correlated with the regional lymph node status and disease stage (P < 0.05). The levels of MICA protein and mRNA expression differ among normal oral mucosa, para-cancerous tissue, and cancerous tissue. MICA may contribute to the tumorigenesis and progression of OSCC.

The Anti-tumor Activity of Vitamin C via the Increase of Fas (CD95) and MHC I expression on Human Stomach Cancer Cell Line, SNU1

  • Yu, Yeon-Sil;Bae, Se-Yeon;Kim, Hye-Min;Kim, Ye-Jin;Chu, Nag-Bum;Chu, Nag-Kyun;Kang, Jae-Seung;Lee, Wang-Jae
    • IMMUNE NETWORK
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    • v.11 no.4
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    • pp.210-215
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    • 2011
  • It is already known that high concentration of vitamin C induces apoptosis on tumor cells. However, there is no report regarding the function of vitamin C on the modulation of immune susceptibility of cancer. Therefore, we investigated whether vitamin C can modulate immune susceptibility of tumor cells, especially on the induction of Fas-mediated apoptosis. First, the optimal concentration of vitamin C, which cannot induce damages on tumor cells for 36 hrs. We found that 2 mM of vitamin C did not show harmful effect. In addition, the optimal concentration of agonistic anti-Fas Abs for 18 hrs was examined. As a result, 400 ng/ml of agonistic anti-Fas Abs did not induce apoptosis on tumor cells. Next, we tried to find the effect of 2 mM of vitamin C on the modulation of the susceptibility to agonistic anti-Fas Abs. When tumor cells were cultured with 400 ng/ml of agonistic anti-Fas Abs for 18 hrs, after pre-treatment with 2 mM of vitamin C for 24 hrs, viability of cells was decreased. Interestingly, we found that the expression of Fas (CD95) and MHC class I was increased by the treatment of vitamin C. Taken together, vitamin C increases the susceptibility of tumor cells to anti-Fas Abs and the expression of Fas (CD95) and MHC class I on tumor cells.

Induction of Peptide-specific CTL Activity and Inhibition of Tumor Growth Following Immunization with Nanoparticles Coated with Tumor Peptide-MHC-I Complexes

  • Sang-Hyun Kim;Ha-Eun Park;Seong-Un Jeong;Jun-Hyeok Moon;Young-Ran Lee;Jeong-Ki Kim;Hyunseok Kong;Chan-Su Park;Chong-Kil Lee
    • IMMUNE NETWORK
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    • v.21 no.6
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    • pp.44.1-44.15
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    • 2021
  • Tumor peptides associated with MHC class I molecules or their synthetic variants have attracted great attention for their potential use as vaccines to induce tumor-specific CTLs. However, the outcome of clinical trials of peptide-based tumor vaccines has been disappointing. There are various reasons for this lack of success, such as difficulties in delivering the peptides specifically to professional Ag-presenting cells, short peptide half-life in vivo, and limited peptide immunogenicity. We report here a novel peptide vaccination strategy that efficiently induces peptide-specific CTLs. Nanoparticles (NPs) were fabricated from a biodegradable polymer, poly(D,L-lactic-co-glycolic acid), attached to H-2Kb molecules, and then the natural peptide epitopes associated with the H-2Kb molecules were exchanged with a model tumor peptide, SIINFEKL (OVA257-268). These NPs were efficiently phagocytosed by immature dendritic cells (DCs), inducing DC maturation and activation. In addition, the DCs that phagocytosed SIINFEKL-pulsed NPs potently activated SIINFEKL-H2Kb complex-specific CD8+ T cells via cross-presentation of SIINFEKL. In vivo studies showed that intravenous administration of SIINFEKL-pulsed NPs effectively generated SIINFEKL-specific CD8+ T cells in both normal and tumor-bearing mice. Furthermore, intravenous administration of SIINFEKL-pulsed NPs into EG7.OVA tumor-bearing mice almost completely inhibited the tumor growth. These results demonstrate that vaccination with polymeric NPs coated with tumor peptide-MHC-I complexes is a novel strategy for efficient induction of tumor-specific CTLs.